title: No regional difference in dopamine D2 receptor occupancy by the second-generation antipsychotic drug risperidone in humans: a positron emission tomography study.
abstract: The effects of antipsychotic drugs have generally been considered to be mediated by blockade of dopamine D2 receptors. The concept of limbic and cortical selectivity of second-generation antipsychotics, i.e. higher dopamine D2 receptor occupancy in the cerebral cortices than in the striatum, has been suggested to explain their clinical efficacy with lower incidence of extrapyramidal side-effects. In this study, regional distribution of dopamine D2 receptor occupancy by risperidone was determined in order to elucidate the limbic and cortical selectivity of second-generation antipsychotics. Striatal and extrastriatal dopamine D2 receptor binding at baseline and after oral administration of 2 mg risperidone were measured in ten healthy men by positron emission tomography (PET) using different tracers with different affinity for the receptors, [11C]raclopride and [11C]FLB 457, respectively. Striatal and extrastriatal occupancies of dopamine D2 receptors were calculated for each brain region. Occupancies of dopamine D2 receptors were about 70% and 60% in the striatum and extrastriatum, respectively. A simulation study showed that non-negligible specific binding in the reference region (cerebellum), could cause systemic underestimation of occupancy in [11C]FLB 457 PET studies, indicating that occupancies in both the striatum and extrastriatum may not have differed. Among the extrastriatal regions including limbic and neocortical regions, no significant regional differences in dopamine D2 receptor occupancy were observed. Thus, limbic and cortical selectivity was not observed by one of the second-generation antipsychotics, risperidone.
authors.affiliation: Clinical Neuroimaging Team, Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. hito@nirs.go.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Arakawa
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Takahashi
authors.forename: Harumasa
authors.initials: H
authors.lastname: Takano
authors.forename: Masaki
authors.initials: M
authors.lastname: Okumura
authors.forename: Tatsui
authors.initials: T
authors.lastname: Otsuka
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikoma
authors.forename: Miho
authors.initials: M
authors.lastname: Shidahara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018967:Risperidone / Q000378:metabolism* / Q000494:pharmacology; D055815:Young Adult
chemical_list: D017448:Receptors, Dopamine D2; D018967:Risperidone